A Core Genome Approach That Enables Prospective and Dynamic Monitoring of Infectious Outbreaks

Whole-genome sequencing is increasingly adopted in clinical settings to identify pathogen transmissions, though largely as a retrospective tool. Prospective monitoring, in which samples are continuously added and compared to previous samples, can generate more actionable information. To enable prospective pathogen comparison, genomic relatedness metrics based on single-nucleotide differences must be consistent across time, efficient to compute and reliable for a large variety of samples. The choice of genomic regions to compare, i.e., the core genome, is critical to obtain a good metric. We propose a novel core genome method that selects conserved sequences in the reference genome by comparing its k-mer content to that of publicly available genome assemblies. The conserved-sequence genome is sample set-independent, which enables prospective pathogen monitoring. Based on clinical data sets of 3436 S. aureus, 1362 K. pneumoniae and 348 E. faecium samples, ROC curves demonstrate that the conserved-sequence genome disambiguates same-patient samples better than a core genome consisting of conserved genes. The conserved-sequence genome confirms outbreak samples with high sensitivity: in a set of 2335 S. aureus samples, it correctly identifies 44 out of 44 known outbreak samples, whereas the conserved-gene method confirms 38 known outbreak samples

Antimicrobial Use in COVID-19 Patients in the First Phase of the SARS-CoV-2 Pandemic:A Scoping Review

This scoping review provides new evidence on the prevalence and patterns of global antimicrobial use in the treatment of COVID-19 patients; identifies the most commonly used antibiotics and clinical scenarios associated with antibiotic prescribing in the first phase of the pandemic; and explores the impact of documented antibiotic prescribing on treatment outcomes in COVID-19 patients. The review complies with PRISMA guidelines for Scoping Reviews and the protocol is registered with the Open Science Framework. In the first six months of the pandemic, there was a similar mean antibiotic prescribing rate between patients with severe or critical illness (75.4%) and patients with mild or moderate illness (75.1%). The proportion of patients prescribed antibiotics without clinical justification was 51.5% vs. 41.9% for patients with mild or moderate illness and those with severe or critical illness. Comparison of patients who were provided antibiotics with a clinical justification with those who were given antibiotics without clinical justification showed lower mortality rates (9.5% vs. 13.1%), higher discharge rates (80.9% vs. 69.3%), and shorter length of hospital stay (9.3 days vs. 12.2 days). In the first 6 months of the pandemic, antibiotics were prescribed for COVID-19 patients regardless of severity of illness. A large proportion of antibiotic prescribing for mild and moderate COVID-19 patients did not have clinical evidence of a bacterial co-infection. Antibiotics may not be beneficial to COVID-19 patients without clinical evidence of a bacterial co-infection

Treatment of vulval condyloma with a combination of paiteling and cryotherapy, and its effect on late recurrence

Purpose: To study the clinical effectiveness of a combination of Paiteling and cryotherapy in the treatment of vulval condyloma acuminatum (VCA), and its effect on late recurrence. Methods: Eighty-six VCA patients were chosen as research subjects, and were randomized into group A and group B. Group A patients were treated with combination of Paiteling and cryotherapy, while group B patients received cryotherapy only. The clinical effects of the two treatment methods on VCA were evaluated by measuring area of damaged skin, levels of interleukin-6 (IL-6) and C-reactive protein (CRP), as well as degree of recurrence of VCA in the two groups, before and after treatment. Results: Total clinical treatment effectiveness in group A was significantly higher compared with group B (p < 0.05). After treatment, the area of damaged skin, and levels of IL-6 and CRP were markedly lower in group A than in group B (p < 0.001). After 6 months of treatment, disease control was higher in group A than in group B (p < 0.05). There was also a lower incidence of adverse reactions in group A than in group B (p < 0.05). Conclusion: These results indicate that the combination of Paiteling and cryotherapy is more effective than cryotherapy alone in improving treatment effectiveness and reducing late recurrence of VCA. Therefore, the combined treatment has potentials clinical application in the management of VCA

Evolution and Mutations Predisposing to Daptomycin Resistance in Vancomycin-Resistant Enterococcus faecium ST736 Strains

We recently identified a novel vancomycin-resistant Enterococcus faecium (VREfm) clone ST736 with reduced daptomycin susceptibility. The objectives of this study were to assess the population dynamics of local VREfm strains and genetic alterations predisposing to daptomycin resistance in VREfm ST736 strains. Multilocus sequence typing and single nucleotide variant data were derived from whole-genome sequencing of 250 E. faecium isolates from 1994-1995 (n = 43), 2009-2012 (n = 115) and 2013 (n = 92). A remarkable change was noticed in the clonality and antimicrobial resistance profiles of E. faecium strains between 1994-1995 and 2013. VREfm sequence type 17 (ST17), the prototype strain of clade A1, was the dominant clone (76.7%) recognized in 1994-1995. By contrast, clone ST736 accounted for 46.7% of VREfm isolates, followed by ST18 (26.1%) and ST412 (20.7%) in 2013. Bayesian evolutionary analysis suggested that clone ST736 emerged between 1996 and 2009. Co-mutations (liaR.W73C and liaS.T120A) of the liaFSR system were identified in all ST736 isolates (n = 111, 100%) examined. Thirty-eight (34.2%) ST736 isolates exhibited daptomycin-resistant phenotype, of which 13 isolates had mutations in both the liaFSR and cardiolipin synthase (cls) genes and showed high level of resistance with a daptomycin MIC50 of 32 mug/mL. The emergence of ST736 strains with mutations predisposing to daptomycin resistance and subsequent clonal spread among inpatients contributed to the observed high occurrence of daptomycin resistance in VREfm at our institution. The expanding geographic distribution of ST736 strains in other states and countries raises concerns about its global dissemination

Enterovirus D68 subclade B3 Strain Circulating and Causing an Outbreak in the United States in 2016

In 2014 the United States experienced a nationwide outbreak of Enterovirus D68 (EV-D68) infection. There were no confirmed cases of EV-D68 in 2015 and CDC was only aware of limited sporadic EV-D68 detection in the US in 2016. In this report, we analyzed 749 nasopharyngeal (NP) specimens collected in 2015 and 2016 from patients in the Lower Hudson Valley, New York using a previously validated EV-D68-specific rRT-PCR assay. EV-D68 was detected in none of 199 NP specimens collected in 2015, and in one of 108 (0.9%) samples from January to May and 159 of 442 (36.0%) samples from July to October 2016. Complete EV-D68 genome sequences from 22 patients in 2016 were obtained using a metagenomic next-generation sequencing assay. Comparative genome analysis confirmed that a new EV-D68 strain belonging to subclade B3, with 3.2-4.8% divergence in nucleotide from subclade B1 strains identified during the 2014 US outbreak, was circulating in the US in 2016 and caused an outbreak in the Lower Hudson Valley, New York with 160 laboratory-confirmed cases. Our data highlight the genetic variability and capacity in causing outbreak by diverse EV-D68 strains, and the necessity of awareness and more surveillance on their active circulation worldwide

MRSA Causing Infections in Hospitals in Greater Metropolitan New York: Major Shift in the Dominant Clonal Type Between 1996 and 2014

A surveillance study in 1996 identified the USA100 clone (ST5/SCCmecII)-also known as the New York/Japan clone-as the most prevalent MRSA causing infections in 12 New York City hospitals. Here we update the epidemiology of MRSA in seven of the same hospitals eighteen years later in 2013/14. Most of the current MRSA isolates (78 of 121) belonged to the MRSA clone USA300 (CC8/SCCmecIV) but the USA100 clone-dominant in the 1996 survey-still remained the second most frequent MRSA (25 of the 121 isolates) causing 32% of blood stream infections. The USA300 clone was most common in skin and soft tissue infections (SSTIs) and was associated with 84.5% of SSTIs compared to 5% caused by the USA100 clone. Our data indicate that by 2013/14, the USA300 clone replaced the New York/Japan clone as the most frequent cause of MRSA infections in hospitals in Metropolitan New York. In parallel with this shift in the clonal type of MRSA, there was also a striking change in the types of MRSA infections from 1996 to 2014

Complete Genome Sequences of Four Toxigenic ;Clostridium difficile Clinical Isolates from Patients of the Lower Hudson Valley, New York, USA

Complete genome sequences of four toxigenic Clostridium difficile isolates from patients in the lower Hudson Valley, New York, USA, were achieved. These isolates represent four common sequence types (ST1, ST2, ST8, and ST42) belonging to two distinct phylogenetic clades. All isolates have a 4.0- to 4.2-Mb circular chromosome, and one carries a phage

Emergence and Evolution of Multidrug-Resistant Klebsiella pneumoniae with both blaKPC and blaCTX-M Integrated in the Chromosome

The extended-spectrum-β-lactamase (ESBL)- and Klebsiella pneumoniaecarbapenemase (KPC)-producing Enterobacteriaceae represent serious and urgent threats to public health. In a retrospective study of multidrug-resistant K. pneumoniae, we identified three clinical isolates, CN1, CR14, and NY9, carrying both blaCTX-M and blaKPC genes. The complete genomes of these three K. pneumoniae isolates were de novo assembled by using both short- and long-read whole-genome sequencing. In CR14 and NY9, blaCTX-M and blaKPC were carried on two different plasmids. In contrast, CN1 had one copy of blaKPC-2 and three copies of blaCTX-M-15 integrated in the chromosome, for which the blaCTX-M-15 genes were linked to an insertion sequence, ISEcp1, whereas the blaKPC-2 gene was in the context of a Tn4401a transposition unit conjugated with a PsP3-like prophage. Intriguingly, downstream of the Tn4401a-blaKPC-2-prophage genomic island, CN1 also carried a clustered regularly interspaced short palindromic repeat (CRISPR)-cas array with four spacers targeting a variety of K. pneumoniae plasmids harboring antimicrobial resistance genes. Comparative genomic analysis revealed that there were two subtypes of type I-E CRISPR-cas in K. pneumoniae strains and suggested that the evolving CRISPR-cas, with its acquired novel spacer, induced the mobilization of antimicrobial resistance genes from plasmids into the chromosome. The integration and dissemination of multiple copies of blaCTX-Mand blaKPC from plasmids to chromosome depicts the complex pandemic scenario of multidrug-resistant K. pneumoniae. Additionally, the implications from this study also raise concerns for the application of a CRISPR-cas strategy against antimicrobial resistance

Effect of rotating twisted tape on thermo-hydraulic performances of nanofluids in heat-exchanger systems

Stable TiO2-H2O nanofluids are prepared and their stabilities are studied. An experimental set for studying the heat transfer and flow characteristics of nanofluids is established. Heat transfer and flow characteristics of TiO2-H2O nanofluids in a circular tube with rotating and static built-in twisted tapes are experimentally investigated and compared. An innovative performance evaluation plot of exergy efficiency is developed and the exergy efficiency of tube with rotating and static built-in twisted tapes filled with nanofluids is analyzed in this paper. The results indicate that the combination of rotating built-in twisted tape and TiO2-H2O nanofluids shows an excellent enhancement in heat transfer, which can increase the heat transfer by 101.6% compared with that of in a circular tube. The effects of nanoparticle mass fractions (ω= 0.1%, 0.3% and 0.5%) and Reynolds numbers (Re = 600–7000) on the heat transfer and flow characteristics of TiO2-H2O nanofluids are discussed. It is found that there is a critical Reynolds number (Re = 4500) for the maximum value of relative heat transfer enhancement ratio. The comprehensive performance of the experimental system is analyzed. It can be found that the comprehensive performance index of the experimental system firstly increases and then reduces with Reynolds number, and it can reach 1.519 at best. However, for the performance evaluation of exergy efficiency, the coupling of rotating twisted tape and nanofluids deteriorates the exergy efficiency. Also, it can be found that the exergy efficiency of the circular tube with twisted tape is greater than that of circular tube under the same pumping power and pressure drop, but it shows deterioration under the same mass flow rate